Nanoparticle Diagnostic and Methods for Treating Disease
a technology of nanoparticles and diagnostic methods, applied in the field of in vivo contrast agents in medical imaging, can solve the problem of relative little information about the biodistribution of nanoparticles in patients, and achieve the effect of increasing the accumulation of nanoparticles and increasing the density of nanoparticles
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example 1
EPR Evaluation and Treatment of a Patient with Metastatic Lung Cancer
[0145]A patient with primary lung cancer that has progressed to metastatic stage will be indicated for treatment with compound 1 encapsulated in PLGA-PEG nanoparticles (1-NP).
[0146]Imaging studies including PET scan will show two metastatic lesions around the dorsal root compressing the nerves. The compression of the nerves will cause a foot-drop syndrome in the patient.
[0147]To assess the EPR effect in the tumor sites, 102 mg of ferumoxytol is administered to the patient as a one time bolus. After an equilibration period of 90 minutes, the patient is imaged using MRI with both T1 and T2 imaging modalities. Assessment of the MRI image by a board-certified radiologist establishes that ferumoxytol had penetrated into all the tumor sites and the relative intensity of the ferumoxytol-associated image (ferumoxytol density) at the tumor site as compared to the surrounding tissue is greater than 10 to 1, with the metastat...
example 2
EPR Evaluation and Treatment of a Patient with Metastatic Colon Cancer
[0152]A patient with colon cancer that has previously been treated with one course of oxaliplatin is found to have progressive disease. While the primary tumor is stable, there are multiple metastases with two metastatic nodes, specifically, in the distal colon, that have aggressive growth rates. The treating oncologist is determining whether to initiate a new round of oxaliplain treatment in the form of a nanoparticle forrmulation of DACH-platin in PEG-PGLA nanoparticles (NPDP) or a whether to perform a radical colectomy. The NPDP is in the 40-50 nM size range and the DACH is conjugated to the PEG-PGLA.
[0153]To predict whether the patient will respond to the NPDP treatment, the oncologist refers the patient to a radiologist to assess the EPR effect in each of the tumor sites using ferumoxtran-10 (Combidex, Sinerem) iron oxide particles as a diagnostic agent. MRI assessment after ferumoxtran-10 infusion demonstrat...
example 3
Synthesis of Polymeric Nanoparticles
Synthesis of Polylactide-Cyanine7 Conjugate Polymer
[0155]
[0156]A flask was charged with polylactide polymer (PLA25) (525 mg, 0.0210 mmol), COMU (9.50 mg, 0.0232 mmol) and Cyanine7 amine (19.0 mg, 0.0232 mmol). DMF (5 mL) and diisopropylamine (0.10 mL) were added, and the reaction stirred in the dark at room temperature for 20 h. All solvent was removed in vacuo, and the remaining material dissolved in ethyl acetate (4 mL). This solution was added dropwise to a vial of 0 isopropanol (60 mL) with rapid stirring. The resulting suspension was centrifuged, and the supernatant decanted. This dissolve / precipitate / centrifuge sequence was repeated another two times, until very little green color was seen in the supernatant. After the final centrifugation, the remaining material was taken up in acetonitrile (5 mL), cooled to 0° C., and water (2 mL) was added. The solution was quickly frozen, and lyophilized to give polylactide-Cy7 conjugate polymer (230 mg,...
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